The noble laureate in Physiology or medicine 1958, Joshua Lederberg had coined the term "microbiome" in the year 2001 to describe the biological community of pathogenic, commensal, and symbiotic microorganisms that live inside living organism. About 10-100 trillion symbiotic microbial cells are carried by each individual, mostly in the gut, that are known as the human microbiota. While the term "human microbiome" refers to the genetic material of microorganisms (microbiota) that live at a specific location within the human body. Numerous anatomical body locations, including the skin, mucosa, gastrointestinal system, respiratory tract, urogenital tract, and mammary gland, are colonized by microorganisms. The human microbiome plays a critical role in immunity, metabolism, and nutritional extraction. It is also essential for the creation of bioactive compounds including lipids, vitamins, and amino acids.[1]
Why human micro biome holds importance in research?
Recent research have highlighted the function of gut microbiota and its metabolites in modifying therapy results in human diseases. The drug-microbiota interaction is known to cause individual variability in drug response (IVDR) or adverse drug reactions (ADR). Numerous sub-disciplines have emerged from this topic, such as pharmacomicrobiomics, pharmacometabonomics, and pharmacometagenomics.These subfields seek to investigate how microbiota variation impacts IVDR in human disorders as well as the impact of microbiome on PK and PD. The National Institutes of Health (NIH) launched the Human Microbiome Project (HMP) in 2007 as a cooperative initiative to thoroughly investigate the diversity and functions of the human microbiota. The project intends to examine the role of microbiota in IVDR, characterize microbiota from diverse body regions in humans using highthroughput sequencing techniques, and provide new research tools and resources for the scientific community. The term "pharmacomicrobiomics" was coined in 2010 to characterize the impact of changes in the composition and function of the microbiota on IVDR and host genetics. Microbiome differences have implications for both pharmacomicrobiomics, which studies how different microbiomes affect medication action, toxicity, and disposition, and personalized medicine.[2]
Microbiome factor in drug discovery & development
There are three domains in which the microbiome directly influences drug development:
(1) microbial impacts on drug safety and efficacy,
(2) drug effects on collateral microbiome community restructuring, and
(3) possible adverse effects of novel therapies targeting the microbiome.
Drugs can be significantly changed clinically by the microbiome without the patient knowing, and in the most extreme situations, this can result in deadly drug interactions. The 'canonical' pharmacokinetics of pharmaceuticals can be changed by activating, deactivating, toxifying, or releasing metabolites. For instance, Bacteroides species toxify brivudine using a conserved purine nucleoside phosphorylase, Eggerthella lenta's cgr operon inactivates digoxin, Helicobacter pylori absorbs and inactivates L-dopa, and microbiome β-glucuronidases deconjugate the irinotecan metabolite SN-38G, regenerating the drug's cytotoxic form.[3]
Medication is starting to show up as a significant factor affecting the composition of the human gut microbiome. Although the importance of non-antibiotic medications was not well understood until recently, antibiotics with broad-spectrum effects are also recognized to have a direct effect on our gut microbiota. They therefore result in a variety of gastrointestinal adverse consequences, including infections with Clostridium difficile. The adverse effects of antibiotics on the gut microbiome have drawn increased attention lately. For instance, β-lactams are known to kill bacteria and have strainspecific action, we reasoned that they might produce long-lasting effects on community composition by irreversibly depleting certain members of the microbiota. [4]
Therapeutics of which there are presently nine varieti...
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